Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Functional consequences of the arrhythmogenic G306R KvLQT1 K+ channel mutant probed by viral gene transfer in cardiomyocytes
Autore:
Li, RA; Miake, J; Hoppe, UC; Johns, DC; Marban, E; Nuss, HB;
Indirizzi:
Johns Hopkins Univ, Sch Med, Inst Mol Cardiobiol, Baltimore, MD 21205 USA Johns Hopkins Univ Baltimore MD USA 21205 iobiol, Baltimore, MD 21205 USA
Titolo Testata:
JOURNAL OF PHYSIOLOGY-LONDON
fascicolo: 1, volume: 533, anno: 2001,
pagine: 127 - 133
SICI:
0022-3751(20010515)533:1<127:FCOTAG>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARDIAC POTASSIUM CURRENT; I-KS; BLOCK; ARRHYTHMIAS; DOMINANT; EXCITABILITY; SUPPRESSION; K(V)LQT1; PROTEINS; MYOCYTES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
17
Recensione:
Indirizzi per estratti:
Indirizzo: Marban, E Johns Hopkins Univ, Sch Med, Inst Mol Cardiobiol, 720 Rutland Ave Ross 844, Baltimore, MD 21205 USA Johns Hopkins Univ 720 Rutland Ave Ross844 Baltimore MD USA 21205
Citazione:
R.A. Li et al., "Functional consequences of the arrhythmogenic G306R KvLQT1 K+ channel mutant probed by viral gene transfer in cardiomyocytes", J PHYSL LON, 533(1), 2001, pp. 127-133

Abstract

1. I-K8,I- the slow component of the delayed rectifier potassium current, figures prominently in the repolarization of heart cells. The K+ channel gene KvLQT1 is mutated in the heritable long QT (LQT) syndrome. Heterologous coexpression of KvLQT1 and the accessory protein minK yields I-K8-like current. Nevertheless, the links between KvLQT1 and cardiac I-K8 are largely inferential.2. Since the LQT syndrome mutant KvLQT1-G306R suppresses channel activity when coexpressed with wild-type KvLQT1 in a heterologous system, overexpression of this mutant in cardiomyocytes should reduce or eliminate native I-K8 if KvLQT1 is indeed the major molecular component of this current. To test this idea, we created the adenovirus AdRMGI-KvLQT1-G306R, which overexpresses KvLQT1-G306R channels.3. In > 60% of neonatal mouse myocytes, a sizable I-K8, could be measured using perforated-patch recordings (8.0 +/- 1.6 pA pF(-1), n = 13). I-K8 wasincreased by forskolin and blocked by clofilium or indapamide I,ut not by E-4031. While cells infected with a reporter virus expressing only green fluorescent protein (GFP) displayed I-K8 similar to that in uninfected cells,AdRMGI-KvLQT1-G306R-infected cells showed a significantly reduced I-K8 (2.4 +/- 1.1 pA pF(-1), 10, P< 0.01) when measured 60-72 h after infection. Similar results were observed in adult guinea-pig myocytes (5.9 <plus/minus> 1.2 pA pF(-1), n = 9, for control vs. 0.1 +/- 0.1 pA pF(-1), n = 5, for AdRMGI-KvLQT1-G306R-infected cells).4. We conclude that KvLQT1 is the major molecular component of I-K8. Our results further establish a dominant-negative mechanism for the G306R LQT syndrome mutation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 00:20:07